The skeletal system of humans and animals consists of bones and joints to which are attached muscles, tendons and ligaments. Bones are the principal organs of support and protection for the body. Joints are the places at which two bones meet (articulate). Because bones are incapable of movement without the help of muscles, contraction must be provided by muscular tissue. In the skeleton, muscles are usually attached to two articulating bones, and during contraction, one bone is drawn toward another. Muscles, therefore produce movement by exerting a force on the bones to which they are attached.
Bones consist of mineral deposits embedded with living cells that must continually receive food and oxygen. Bones generally consist of the following parts: the diaphysis; the epiphyses; and articular cartilage. The diaphysis is the shaft or long main portion of the bone. This part of the bone consists mainly of compact bone. The epiphyses are the two ends or extremities of the bone. In the long bones, the epiphyses have a bulbous shape to provide space for muscle and ligament attachments near the joints. Articular cartilage is a thin layer of resilient hyaline cartilage. The elasticity of the hyaline cartilage provides the joints with a cushion against jars and blows.
To allow body movements, all bones must have articulating surfaces. These surfaces form joints, or articulations, with various degrees of mobility. Some are freely movable (diarthroses); others are only slightly movable (amphiarthroses); and the remaining are totally immovable (synarthroses). All three types are necessary for smooth, coordinated body movements.
Every joint is covered with connective tissue and cartilage. The ligaments and connective tissue in these areas permit bones to be connected to each other. Muscles attached to freely movable joints permit a great deal of body movement. The synovial membrane that lines the joint cavity secretes synovial fluid, which acts as a lubricant of the joints. The bones in a synovial joint are separated by a joint capsule. The joint capsule is strengthened by ligaments (fibrous bands, or sheets, of connective tissue) that often anchor bones to each other. All of the above factors working together in a complementary manner make various body movements possible.
Thus, the joints of humans and animals comprise two or more bone surfaces that are in constant contact with each other. These surfaces slide against each other as the bones are moved. Because the pressures on the surfaces can be enormous and the movement is constant, a highly efficient lubricating system is necessary to prevent the deterioration of the bone surface. This is done naturally by coating the contacting surfaces with a layer of collagen-like material which reduces the friction caused by the constant contact and motion between the surfaces. In addition a natural aqueous lubricating liquid, called synovial fluid, is normally present which further reduces the friction between the surfaces in the joint.
The aqueous lubricating synovial fluid is a solution containing a heteropolysaccharide such as hyaluronic acid. Hyaluronic acid contains alternating residues of two different sugar units. These alternating units are normally D-glucuronic acid and N-acetyl-D-glucosamine. Hyaluronic acid forms a highly viscous jelly-like solution which is ideal for lubricating a joint in an animal or human.
In certain abnormal conditions, the natural lubricating fluid is present in abnormally low amounts resulting in painful joints. In these conditions, it is common to prepare a solution of hyaluronic acid, collagen, or other types of synthetic or natural high-viscosity material. These solutions are then injected into the abnormal joint to aid in the lubrication of the joint surfaces during movement.
Aqueous solutions of water-soluble viscoelastic polymers have been widely used to lubricate joints such as knee joints, spinal cord or other areas of the body. These solutions minimize physical trauma due to surface abrasion. In the joints, the solutions lubricate the contact surfaces as the synovial fluid does in the normal joints. Traditionally, a dilute solution (0.1 to 5% w/v) has been used for handling convenience. Because the concentrated aqueous solution is an extremely viscous gel, it is quite difficult to inject the material through a 14-gauge needle.
Thus, a major problem in administering these solutions is the extremely high viscosity of the solutions. It is very difficult to inject high concentrations or large amounts of these viscous materials into body tissues, such as joints or urethral soft tissues. Very large gauge needles are required to administer sufficient quantities of the the fluid to the intended body part. This results in extreme discomfort to the human or animal to which the fluid is being administered. Depending on the compound used and the concentration of the compound, the injectability of the suspension may be less than adequate. Such inadequacy may manifest itself in terms of difficulties in extruding the suspension through a fine gauge needle and/or poor intrusion into the tissue. Common extrusion difficulties are excessive or irregular extrusion pressures and needle blockage.
What is needed is a delivery system that will enable the physician or veterinarian to inject the lubricating material in relatively small volumes using small gauge needles. Ideally, the delivery system should include a solution which is not viscous, but will develop desired physical properties after it has been delivered to the desired site in the body.